On the assumption that physical dependence is an important aspect of abuse liability, several sedative-hypnotic drugs will be quantitatively compared with respect to their potency in eliciting physical dependence. The main drugs to be tested are barbiturates, benzodiazepines, meprobamate and methaqualone. We will develop assay methods, including gas chromatography and EMIT techniques, of sufficient sensitivity to detect these drugs in small samples of mouse tail blood. The drugs will be chronically administered in mice by methods designed to maintain stable blood concentrations in the range that produces ataxia. Withdrawal reactions will be rated quantitatively. A hypothesis to be tested is that several drugs of the "alcohol-barbiturate" group produce physical dependence by the same neuronal mechanism. The time course and dose relations of physical dependence will be estimated for each drug. We will compare drug responses in mouse strains of different genetic background. Cross-dependence will be investigated. We will examine the relationship between the rate of drug disappearance from the body and the severity of withdrawal reactions. Where possible, we will modify the elimination rates to see whether a faster elimination produces a more severe withdrawal reaction.